Prostaglandins and cyclic nucleotides appear to be important regulators of immune inflammatory responses. Prostaglandins appear to influence cell function via effects on cyclic nucleotides. The prostaglandin-cyclic nucleotide relationship will be studied in leucocytes (synovial fluid, blood) of patients with rheumatoid arthritis and systemic lupus erythematosus, and correlated with disease activity. The prostaglandin-cyclic nucleotide interactions will also be studied in synovial cells (RA, normal) maintained in tissue culture. An analysis will be made of the endocytic-degradative function of synovial lining cells to determine if impaired clearance mechanisms in RA synovial cells lead to increased release of mediators of inflammation. In polymorphonuclear leucocytes from patients with Chediak-Higashi syndrome there appears to be a defect in microtuble assembly. An effort will be made to determine whether the defect is due to altered amounts or type of tubulin synthesized by CH cells or to a defect in generation of, or response to, cyclic GMP. Experimental animal models exist for SLE and the CH syndrome. The two models have features in common, and both are improved after treatment with compounds which in vitro influence cyclic nucleotide concentrations in leucocytes and other tissues. The compounds will be administered to the animals and their effect on the course of the disease and on immune responses in these animals will be investigated.